Anne Le, M.D., M.Sc.
Primary Appointment in Pathology
My research is primarily focused on cancer metabolism, specifically studying the key enzymes of glycolysis and glutaminolysis: lactate dehydrogenase A and glutaminase. My research has shown that the inhibition of these enzymes induced oxidative stress thereby inhibiting tumor progression, demonstrating that targeting these metabolic processes can be used in the near future as a feasible cancer therapy. Using a Metabolomics approach, my laboratory is defining the factors that predict the sensitivity of pancreatic cancers to current chemotherapies and also to our novel small drug-like molecules. Our goal is to characterize and enable targeted selection of patients based upon predicted metabolic response. Furthermore in this pursuit, we have developed an innovative dual fluorescent protein reporter, termed HypoxCR, which can simultaneously detect cells that are hypoxic and/or cycling to study the effects of the tumor's microenvironment on the sensitivity to metabolic inhibitors.
Le A, Lane NA, Hamaker M, Bose S, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H, Zimmerman LJ, Liebler DC, Slebos R, Lorkiewicz P, Higashi RM, Fan WMT and Dang CV. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in human B lymphocytes. (Co-corresponding author). Cell Metab. 2012 Jan 4;15(1):110-21.
Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, Deck LM, Royer RE, Vander Jagt DL, Semenza GL, Dang CV. Inhibition of Lactate Dehydrogenase A Induces Oxidative Stress and Inhibits Tumor Progression. Proc Natl Acad Sci U S A. 2010 Feb 2; 107(5):2037-42.
Yustein J, Liu Y, Gao P, Jie C, Le A, Vuica-Ross M, Chng W, Eberhart C, Bergsagel L, Dang CV. Induction of ectopic Myc target gene, JAG2, augments hypoxic growth and tumorigenesis in a human B cell model. Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3534-9.
Dang CV, Le A, Gao P. MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res. 2009 Nov 1; 15(21):6479-83.
Le A, Zielinski R, He C, Crow MT, Biswal S, Tuder RM, Becker PM. Pulmonary epithelial neuropilin-1 deletion enhances development of cigarette smoke-induced emphysema. Am J Respir Crit Care Med. 2009 Sep 1; 180(5):396-406 (Cover image).